This application is a 371 of PCT/IT99/00364 filed Nov. 11, 1999.
The present invention relates to complexes of hyaluronic acid and xe2x80x9ccarnitinesxe2x80x9d, the latter herein meaning both carnitine as it is and, more specifically, its acyl derivatives with straight or branched chain aliphatic carboxylic acids, optionally unsaturated or polyunsaturated, containing 2 to 20 carbon atoms.
Although the complexes according to the invention can contain, as carnitine component, DL-carnitine or D and L carnitine mixtures in variable ratios, as well as the related acyl derivatives as stated above, the preferred embodiment relates to complexes of hyaluronic acid and L-carnitine or acyl-L-carnitine, wherein xe2x80x9cacylxe2x80x9d has the meanings defined above. In the present invention, xe2x80x9ccarnitinexe2x80x9d will therefore mean, unless otherwise stated, L-carnitine; the same applies for the various acylcarnitines which will be cited in the following.
xe2x80x9cHyaluronic acidxe2x80x9d will herein mean a hyaluronic acid of molecular weight ranging from about 2xc3x97103 to about 5xc3x97106, preferably from about 2xc3x97105 to about 3xc3x97106.
As it is obvious by what stated above, both components of the complexes according to the invention are per se known. Information concerning hyaluronic acid as well as numerous references concerning carnitine (page 281) and acetylcarnitine (page 13), can be found, inter alia, in Merck Index, 11th edition, page 751, 281 and 13, respectively; whereas acylcarnitines and/or the use thereof are the object of a number of patents (see for example U.S. Pat. No. 4,346,107, U.S. Pat. No. 4,194,006, U.S. Pat. No. 4,343,816).
The therapeutical indications of the cited components are also well known. In particular, hyaluronic acid is used as coadjuvant in the treatment of synovitis and tissutal reparation processes.
It now has been found that complexes (or even simple combinations) of hyaluronic acid and xe2x80x9ccarnitinesxe2x80x9d (which means both carnitine as it is and its acyl derivatives) can be in the form of and act as an alimentary supplement or a real medicament, depending on their favourable, preventive or therapeutical action, which said complexes or combinations are intended to exert, depending on the specific end users.
Furthermore, it has been found that said complexes and combinations can be valuable in cosmetics.
The complexes and the combinations indicated above, have, in fact: a) enhanced protective activity on tissues and cell plasmamembrane; b) antiinflammatory and radical-scavenger activities; c) anti-aging activity, in particular restoring- or maintaining-activities on skin elasticity; d) a general trophic, cosmetically remarkable, action. In particular, the complexes and the combinations according to the invention are suitable for the treatment of synovitis and gonarthrosis, Crohn""s disease, ulcerous rectocolitis and celiac disease. Said activities can be more or less marked, depending on the single xe2x80x9ccarnitinexe2x80x9d used.
Therefore a further object of the invention are pharmaceutical and cosmetic compositions containing as active ingredient: a) combinations of hyaluronic acid and carnitine or acylcarnitine, or b)xe2x80x94according to a preferred aspect of the inventionxe2x80x94complexes of hyaluronic acid and carnitine or acylcarnitine, said combinations and complexes containing the two components in weight ratios ranging from 3:1 to 1:3, preferably in equiponderal ratios.
More particularly, an object of the invention are pharmaceutical compositions containing as active ingredient the combinations a) or the complexes b) above defined, with protective activity on tissues and cell plasmamembrane; with antiinflammatory and radical-scavenger activities; for the therapy of synovitis and gonarthrosis; for the therapy of Crohn"" disease, ulcerous rectocolitis and celiac disease; moreover, cosmetic compositions containing the combinations a) or the complexes b), with anti-aging activity, and restoring- and maintaining-activities on skin elasticity and general trophic action.
As already mentioned, carnitine and acylcarnitines contained in the above mentioned pharmaceutical and cosmetic compositions are preferably L-carnitine and acyl-L-carnitine. Particularly preferred are acetyl-L-carnitine, propionyl-L-carnitine and palmitoyl-L-carnitine.
The complexes of the invention contain the two components in weight ratios ranging form 1:3 to 3:1, preferably in equiponderal ratios. They are obtained by: a) addng hyalluroinic acid to a suspension or solution of acylcarnitine (or carnitine) in ethanol/PBS (phosphate-buffered saline), under stong stirring, at a temperature of 20-60xc2x0 C., preferably about 50xc2x0 C., or b) adding acylcarnitine (or carnitine) to a solution of hyaluronic acid in PBS, subjecting the shole first to sonication at temperatures ranging between 10 and 30xc2x0 C., preferably at 15-20xc2x0 C., thn to centrifugation, with recovery of the supernatant. The resulting product has been proved to be a real complex by means of the chemico-physical detrminations which will be described in the folwing.